This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Although standard diagnostic classifications consider obsessive-compulsive disorder (OCD) to be a single diagnostic entity, it has become clear that several different symptom subtypes of OCD exist. The principal OCD symptom factors are: 1) aggressive obsessions with checking compulsions;2) symmetry obsessions with arranging and repeating compulsions;3) contamination obsessions with cleaning compulsions;and 4) hoarding/saving symptoms. These symptom factors show different genetic inheritance, comorbidity, and treatment response. But since virtually all prior studies of OCD have grouped patients with diverse symptom patterns together, it is not known whether OCD symptom factors differ from one another in terms of pathophysiology. Hoarding/saving symptoms, found in 20% - 42% of OCD patients, are part of a discrete clinical syndrome that includes information-processing deficits and difficulty with decision-making. It can cause severe disability and is a strong predictor of poor response to standard treatments for OCD. A better understanding of the neurobiology of compulsive hoarding is required to develop more effective treatments for this syndrome. Yet, despite its common occurrence and clinical significance, no study to date has investigated the neurobiology of obsessive-compulsive hoarding in humans. Pilot functional neuroimaging data from our research team suggest that patients with the compulsive hoarding syndrome have significantly lower rates of glucose metabolism in the anterior and posterior cingulate gyrus than normal controls and non-hoarding OCD patients, and that cingulate metabolism is negatively correlated with the severity of compulsive hoarding/saving symptoms. The objectives of the proposed research are to confirm and extend these preliminary findings in a more definitive study with a larger and more homogeneous sample of subjects selected prospectively, and also to identify structural neuroanatomical and neurocognitive abnormalities associated with the compulsive hoarding syndrome. This study will compare age- and sex-matched groups of 24 compulsive hoarders, 24 non-hoarding OCD patients, and 24 normal controls, using [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) to measure cerebral glucose metabolism, quantitative magnetic resonance imaging to measure regional brain volumes and morphology, and neuropsychological testing to measure cognitive deficits, before and after standardized treatment with a serotonin reuptake inhibitor (SRI). The long-term goal is to develop more effective treatments for compulsive hoarding, based on an improved understanding of its pathophysiology.